High-dose irinotecan plus LV5FU2 or simplified LV5FU (HD-FOLFIRI) for patients with untreated metastatic colorectal cancer: a new way to allow resection of liver metastases?

Oncology. 2008;74(1-2):17-24. doi: 10.1159/000138352. Epub 2008 Jun 9.


The antitumor efficacy of irinotecan may be dose dependent. This study aimed to determine the safety and efficacy of high-dose (HD) irinotecan combined with LV5FU2 or simplified LV5FU (LV5FUs) in first-line treatment of metastatic colorectal cancer.

Patients and methods: Patients with unresectable and measurable metastatic colorectal cancer, not pretreated for metastatic disease, were given irinotecan 260 mg/m(2) combined with LV5FU2 in the first 25 patients, then with LV5FUs (HD-FOLFIRI) in 35 patients. G-CSF was given in case of febrile neutropenia, grade 4 neutropenia >7 days or neutropenia grade >1 at day 15.

Results: The response rate was 57% (95% confidence interval 43-69%). Second surgery with curative intent was performed in 28% of patients, leading to 20% radiological complete response. Median response duration, time to progression and overall survival were 11, 9 and 22 months, respectively. The median dose intensity of irinotecan was 117 mg/m(2)/week. G-CSF was given to 45% of patients over 33% of cycles. Usual toxicity of irinotecan and 5-FU were observed without major increased frequency, except hematological toxicity. Tolerance was similar with LV5FU2 and LV5FUs, though more asymptomatic grade 3-4 neutropenia was observed with LV5FU2.

Conclusion: HD-irinotecan plus LV5FU2 or HD-FOLFIRI is feasible and achieved a high response rate and postsurgery complete response rate.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Dose-Response Relationship, Drug
  • Female
  • Fluorouracil / administration & dosage
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoadjuvant Therapy
  • Survival Analysis
  • Treatment Outcome


  • Granulocyte Colony-Stimulating Factor
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol